Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25–50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and pharmacokinetic properties with the aim of developing a clinical agent

WFPC2 Observations of NGC 454: an Interacting Pair of Galaxies

We present WFPC2 images in the F450W, F606W and F814W filters of the interacting pair of galaxies NGC 454. Our data indicate that the system is in the early stages of interaction. A population of young star-clusters has formed around the late component, and substantial amounts of gas have sunk into the center of the earlier component, where it has not yet produced significant visible star formation or nuclear activity. We have photometric evidence that the star-clusters have strong line emission, which indicate the presence of a substantial component of hot, massive stars which formed less than 5-10 Myrs ago.Comment: 14 pages, 4 figures, Latex (AAS macros), ApJL in pres

On the embeddability of certain infinitely divisible probability measures on Lie groups

We describe certain sufficient conditions for an infinitely divisible probability measure on a class of connected Lie groups to be embeddable in a continuous one-parameter convolution semigroup of probability measures. (Theorem 1.3). This enables us in particular to conclude the embeddability of all infinitely divisible probability measures on certain Lie groups, including the so called Walnut group (Corollary 1.5). The embeddability is concluded also under certain other conditions (Corollary 1.4 and Theorem 1.6).Comment: 24 page

The star-forming content of the W3 giant molecular cloud

We have surveyed a ~0.9-square-degree area of the W3 giant molecular cloud and star-forming region in the 850-micron continuum, using the SCUBA bolometer array on the James Clerk Maxwell Telescope. A complete sample of 316 dense clumps was detected with a mass range from around 13 to 2500 Msun. Part of the W3 GMC is subject to an interaction with the HII region and fast stellar winds generated by the nearby W4 OB association. We find that the fraction of total gas mass in dense, 850-micron traced structures is significantly altered by this interaction, being around 5% to 13% in the undisturbed cloud but ~25 - 37% in the feedback-affected region. The mass distribution in the detected clump sample depends somewhat on assumptions of dust temperature and is not a simple, single power law but contains significant structure at intermediate masses. This structure is likely to be due to crowding of sources near or below the spatial resolution of the observations. There is little evidence of any difference between the index of the high-mass end of the clump mass function in the compressed region and in the unaffected cloud. The consequences of these results are discussed in terms of current models of triggered star formation.Comment: 13 pages, 8 figures, 1 table (full source table available on request). Accepted for publication in Monthly Notices of the Royal Astronomical Society (Main Journal

Phase diagram and isotope effect in (PrEu)_0.7Ca_0.3CoO_3 cobaltites exhibiting spin-state transitions

We present the study of magnetization, thermal expansion, specific heat, resistivity, and a.c. susceptibility of (Pr$_{1-y}$Eu$_y$)$_{0.7}$Ca$_{0.3}$CoO$_3$ cobaltites. The measurements were performed on ceramic samples with $y = 0.12 - 0.26$ and $y = 1$. Based on these results, we construct the phase diagram, including magnetic and spin-state transitions. The transition from the low- to intermediate-spin state is observed for the samples with $y > 0.18$, whereas for a lower Eu-doping level, there are no spin-state transitions, but a crossover between the ferromagnetic and paramagnetic states occurs. The effect of oxygen isotope substitution along with Eu doping on the magnetic/spin state is discussed. The oxygen-isotope substitution ($^{16}$O by $^{18}$O) is found to shift both the magnetic and spin-state phase boundaries to lower Eu concentrations. The isotope effect on the spin-state transition temperature ($y > 0.18$) is rather strong, but it is much weaker for the transition to a ferromagnetic state ($y < 0.18$). The ferromagnetic ordering in the low-Eu doped samples is shown to be promoted by the Co$^{4+}$ ions, which favor the formation of the intermediate-spin state of neighboring Co$^{3+}$ ions.Comment: 13 pages, including 11 figures, to be published in Phys. Rev.

The Large-scale J=3-2 and J=2-1 CO Emission from M17 and its Implications for Extragalactic CO Observations

We observed a 10x20 pc region of the molecular cloud M17 in the 12CO and 13CO J=3-2 and J=2-1 transitions to determine their global behavior and to assess the reliability of using ratios of CO line intensities integrated over an entire cloud to determine the physical conditions within the cloud. Both the 12CO/13CO J=2-1 and J=3-2 line ratios correlate with the 13CO integrated intensity, with smaller line ratios observed at locations with large integrated intensities. This correlation is likely due to variations in the column density from one position to another within M17. The 12CO and 13CO (J=3-2/J=2-1) line ratios show no significant variation from place to place within M17, even on the peak of the photon-dominated region. A Large Velocity Gradient analysis of globally averaged line ratios gives results in reasonable agreement with the results obtained for individual lines-of-sight through the cloud, which suggests that the typical physical conditions in a molecular cloud can be determined using CO line ratios integrated over the entire cloud. There appears to be a clear trend of increasing 12CO/13CO J=2-1 and J=3-2 line ratios as one moves from Galactic molecular cloud cores to entire Galactic molecular clouds to normal galaxies. The most likely explanation of the high line ratios for normal galaxies is a significant contribution to the CO emission by low column density material, such as diffuse molecular clouds or the outer envelopes of giant molecular clouds.Comment: 26 pages, 6 figures, 2 tables. Accepted for publication in Ap

Narrow Na and K Absorption Lines Toward T Tauri Stars: Tracing the Atomic Envelope of Molecular Clouds

We present a detailed analysis of narrow Na i and K i absorption resonance lines toward nearly 40 T Tauri stars in Taurus with the goal of clarifying their origin. The Na i λ5889.95 line is detected toward all but one source, while the weaker K i λ7698.96 line is detected in about two-thirds of the sample. The similarity in their peak centroids and the significant positive correlation between their equivalent widths demonstrate that these transitions trace the same atomic gas. The absorption lines are present toward both disk and diskless young stellar objects, which excludes cold gas within the circumstellar disk as the absorbing material. A comparison of Na i and CO detections and peak centroids demonstrates that the atomic gas and molecular gas are not co-located, the atomic gas being more extended than the molecular gas. The width of the atomic lines corroborates this finding and points to atomic gas about an order of magnitude warmer than the molecular gas. The distribution of Na i radial velocities shows a clear spatial gradient along the length of the Taurus molecular cloud filaments. This suggests that absorption is associated with the Taurus molecular cloud. Assuming that the gradient is due to cloud rotation, the rotation of the atomic gas is consistent with differential galactic rotation, whereas the rotation of the molecular gas, although with the same rotation axis, is retrograde. Our analysis shows that narrow Na i and K i absorption resonance lines are useful tracers of the atomic envelope of molecular clouds. In line with recent findings from giant molecular clouds, our results demonstrate that the velocity fields of the atomic and molecular gas are misaligned. The angular momentum of a molecular cloud is not simply inherited from the rotating Galactic disk from which it formed but may be redistributed by cloud–cloud interactions

Interstellar Turbulence: II. Energy Spectra of Molecular Regions in the Outer Galaxy

The multivariate tool of Principal Component Analysis (PCA) is applied to 23 fields in the FCRAO CO Survey of the Outer Galaxy. PCA enables the identification of line profile differences which are assumed to be generated from fluctuations within a turbulent velocity field. The variation of these velocity differences with spatial scale within a molecular region is described by a singular power law, delta v= c L^alpha which can be used as a powerful diagnostic to turbulent motions. For the ensemble of 23 fields, we find a mean value alpha = 0.62 +- 0.11. From a recent calibration of this method using fractal Brownian motion simulations (Brunt & Heyer 2001), the measured velocity difference-size relationship corresponds to an energy spectrum, E(k), which varies as k^-beta, where beta = 2.17 +- 0.31. We compare our results to both decaying and forced hydrodynamic simulations of turbulence. We conclude that energy must be continually injected into the regions to replenish that lost by dissipative processes such as shocks. The absence of large, widely distributed shocks within the targeted fields suggests that the energy is injected at spatial scales less than several pc.Comment: 24 pages, 10 figures, accepted by Ap

The linewidth-size relationship in the dense ISM of the Central Molecular Zone

The linewidth (sigma) - size (R) relationship has been extensively measured and analysed, in both the local ISM and in nearby normal galaxies. Generally, a power-law describes the relationship well with an index ranging from 0.2-0.6, now referred to as one of "Larson's Relationships." The nature of turbulence and star formation is considered to be intimately related to these relationships, so evaluating the sigma-R correlations in various environments is important for developing a comprehensive understanding of the ISM. We measure the sigma-R relationship in the Central Molecular Zone (CMZ) of the Galactic Centre using spectral line observations of the high density tracers N2H+, HCN, H13CN, and HCO+. We use dendrograms, which map the hierarchical nature of the position-position-velocity (PPV) data, to compute sigma and R of contiguous structures. The dispersions range from ~2-30 km/s in structures spanning sizes 2-40 pc, respectively. By performing Bayesian inference, we show that a power-law with exponent 0.3-1.1 can reasonably describe the sigma-R trend. We demonstrate that the derived sigma-R relationship is independent of the locations in the PPV dataset where sigma and R are measured. The uniformity in the sigma-R relationship suggests turbulence in the CMZ is driven on the large scales beyond >30 pc. We compare the CMZ sigma-R relationship to that measured in the Galactic molecular cloud Perseus. The exponents between the two systems are similar, suggestive of a connection between the turbulent properties within a cloud to its ambient medium. Yet, the velocity dispersion in the CMZ is systematically higher, resulting in a coefficient that is nearly five times larger. The systematic enhancement of turbulent velocities may be due to the combined effects of increased star formation activity, larger densities, and higher pressures relative to the local ISM.Comment: 11 pages, 8 figures, Accepted for publication in MNRA

Pressure-induced quantum phase transition in Fe₁−ᵪCoᵪSi (x = 0.1,0.2)

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